Classification of environmental factors potentially motivating for dairy cows to access shade.
The aim of this Research Communication was to apply the data mining technique to classify which environmental factors have the potential to motivate dairy cows to access natural shade. We defined two different areas at the silvopastoral system: shaded and sunny. Environmental factors and the frequency that dairy cows used each area were measured during four days, for 8 h each day. The shaded areas were the most used by dairy cows and presented the lowest mean values of all environmental factors. Solar radiation was the environmental factor with most potential to classify the dairy cow's decision to access shaded areas. Data mining is a machine learning technique with great potential to characterize the influence of the thermal environment in the cows' decision at the pasture.


Relative quantification of ERBB2 mRNA in invasive duct carcinoma of the breast: correlation with ERBB-2 protein expression and ERBB2 gene copy number.
The option to treat patients suffering from ERBB-2 protein-positive invasive duct carcinomas of the breast (IDC) with Herceptin requires a precise determination of the ERBB2 status. The aim of the study was to evaluate the ERBB2 mRNA level, placing emphasis on cases with discordant findings between ERBB-2 protein expression (IHC) and a copy number of the ERBB2 gene (FISH). Thirty-nine IDCs (21 cases IHC and FISH concordant, 15 cases moderately discordant, 3 cases markedly discordant) were investigated. ERBB2 mRNA expression was determined using quantitative real-time RT-PCR (Q-RT-PCR). IDCs with negative ERBB-2 protein and without ERBB2 gene amplification had a low ERBB2 mRNA level. Cases with 3+ overexpression of the protein and with strong gene amplification (> 10 copies/tumor cell) had a significantly increased expression of ERBB2 mRNA. In 13 of 15 IDCs with moderate discrepancies (up to 10 copies of the gene per one tumor cell/negative ERBB-2 protein; without amplification/2+ protein) mRNA was low, comparable to that in cases with negative ERBB-2 protein and without ERBB2 gene amplification. In three cases with markedly discordant findings (the gene amplified/protein negative--one case; protein 3+/no amplification--2 cases), Q-RT-PCR results were within a "normal" limit. Ineffective gene amplification and protein accumulation are suggested explanations. Q-RT-PCR revealed two cases with highly expressed ERBB2 mRNA and discordant FISH and/or IHC findings. Increased effectiveness of transcription (protein 2+/high mRNA/without the gene amplification), and combined dysregulation (protein negative/high mRNA/no amplification) are possible causes of these findings. Q-RT-PCR appears useful in clarifying borderline or discrepant IHC and FISH findings.


Improved flow cytometric detection of donor-specific HLA class II antibodies by heat inactivation.
Flow cytometry is a powerful technique for T-cell crossmatching but is prone to false-positive reactions with B cells. In this study the flow cytometry crossmatch (FCXM) was performed in 319 cases, using the patient's serum untreated and incubated at 56 degrees C for 30 minutes. Heat treatment inhibited B-cell reactivity in 30 of 39 cases. Flow cytometry testing with latex beads coated with human leukocyte antigen (HLA) class II antigens showed no class II antibodies in sera that were completely inhibited by heat treatment. There was no inhibition of class I antibodies to either T or B cells, or of class II antibodies to B cells. Experiments with aggregated IgG showed that inhibition by heat treatment is likely due to the prevention of complement binding to aggregates or dissociation of aggregates, or both. We conclude that heat inactivation is a simple step that eliminates false-positive reactions in the B-cell flow cytometry crossmatch.


Investigation of adult stainless steel crown longevity as an interim restoration in pediatric patients.
Preformed metal crowns, also known as stainless steel crowns (SSC), are utilized for providing full coverage to young permanent teeth and have been used extensively as restorations of primary teeth for approximately 65 years. Evaluate permanent tooth SSC longevity as an interim restoration for teeth requiring full coverage restoration in pediatric patients. Retrospective chart review from 2006 through 2014 in a hospital-based dental clinic for permanent tooth pre-fabricated crown longevity. One hundred and fifty-five SSCs were evaluated with regard to: age of patient at restoration placement, diagnoses, and duration of crown service. Duration service was further categorized as successful or failed. Of 155 SSCs, 137 were considered successfully functioning. Total failures were 18. The overall combined success rate for the study group was observed to be 88% with an average service period of 45.18 months. Significant success was noted in patients less than 9 years of age, and significant failure was observed in patients 12 years and older. Stainless steel crowns are a viable option for interim restoration needs, with an 88% overall success rate during an average service period of 45.18 months.


Exponential stability of synchronization in asymmetrically coupled dynamical networks.
Based on the original definition of the synchronization stability, a general framework is presented for investigating the exponential stability of synchronization in asymmetrically coupled networks. By choosing an appropriate Lyapunov function, we prove that the mechanism of the exponential synchronization stability is the asymmetrical coupling matrix with diffusive condition. We deduce the second largest eigenvalue of a symmetric matrix to govern the exponential stability of synchronization in asymmetrically coupled networks. Moreover, we have given the threshold value which can guarantee that the states of the asymmetrically coupled network achieve the exponential stability of synchronization.


Longitudinal variability of phosphorus fractions in sediments of a canyon reservoir due to cascade dam construction: a case study in Lancang River, China.
Dam construction causes the accumulation of phosphorus in the sediments of reservoirs and increases the release rate of internal phosphorus (P) loading. This study investigated the longitudinal variability of phosphorus fractions in sediments and the relationship between the contents of phosphorus fractions and its influencing factors of the Manwan Reservoir, Lancang River, Yunnan Province, China. Five sedimentary phosphorus fractions were quantified separately: loosely bound P (ex-P); reductant soluble P (BD-P); metal oxide-bound P (NaOH-P); calcium-bound P (HCl-P), and residual-P. The results showed that the total phosphorus contents ranged from 623 to 899 µg/g and were correlated positively with iron content in the sediments of the reservoir. The rank order of P fractions in sediments of the mainstream was HCl-P>NaOH-P>residual-P>BD-P>ex-P, while it was residual-P>HCl-P>NaOH-P>BD-P>ex-P in those of the tributaries. The contents of bio-available phosphorus in the tributaries, including ex-P, BD-P and NaOH-P, were significantly lower than those in the mainstream. The contents of ex-P, BD-P, NaOH-P showed a similar increasing trend from the tail to the head of the Manwan Reservoir, which contributed to the relatively higher content of bio-available phosphorus, and represents a high bio-available phosphorus releasing risk within a distance of 10 km from Manwan Dam. Correlation and redundancy analyses showed that distance to Manwan Dam and the silt/clay fraction of sediments were related closely to the spatial variation of bio-available phosphorus.


Tablet formulation of Famotidine-loaded P-gp inhibiting nanoparticles using PLA-g-PEG grafted polymer.
Our work aimed at evaluating the use of permeability glycoprotein (P-gp) inhibiting nanoparticles (NPs) as a part of a suitable oral solid dosage to improve bioavailability. Famotidine (Pepcid®), a stomach acid production inhibitor, was used as a drug model to test our hypothesis. Famotidine-loaded NPs were prepared by solvent emulsion evaporation using PEG grafted on a polylactide acid (PLA) polymer backbone (PLA-g-PEG), with a 5% molar ratio of PEG versus lactic acid monomer and PEG of either 750 or 2000 Da molecular weight. Tablet formulation was composed of 40% Famotidine-loaded NPs, 52.5% microcrystalline cellulose as filler, 7% pre-gelatinized starch as binder/disintegrant, and 0.5% magnesium stearate as lubricant. Tablets containing 1.6 mg of Famotidine were prepared at an average weight of 500 mg, thickness of 6.2-6.5 mm, hardness of 5-8 kp, and disintegration time of <1 min. Our results suggest that Famotidine-loaded NPs using grafted PEG-g-PLA polymers can be formulated as an oral solid dosage form while effectively inhibiting P-gp mediated Famotidine efflux, irrespective of PEG molecular weights. This could therefore represent an attractive formulation alternative to enhance oral permeability and bioavailability of drugs that are P-gp substrates.


Cytotoxic and Noncytotoxic Metabolites from Teratosphaeria sp. FL2137, a Fungus Associated with Pinus clausa.
A new naphthoquinone, teratosphaerone A (1), four new naphthalenones, namely, teratosphaerone B (2), structurally related to 1, iso-balticol B (3), iso-balticol B-4,9-acetonide (4), and (+)-balticol C (5), a new furanonaphthalenone, (3a S,9 R,9a S)-1(9a),3(3a),9-hexahydromonosporascone (6), and the known metabolite monosporascone (7) were isolated from Teratosphaeria sp. FL2137, a fungal strain inhabiting the internal tissue of recently dead but undecomposed foliage of Pinus clausa. The structures of 1-6 were elucidated on the basis of their spectroscopic data including 2D NMR, and absolute configurations of 2, 3, and 6 were determined by the modified Mosher's ester method. When evaluated in a panel of five tumor cell lines, metabolites 1 and 7 isolated from a cytotoxic fraction of the extract exhibited moderate selectivity for metastatic breast adenocarcinoma cell line MDA-MB-231. Of these, 1 showed cytotoxicity to this cell line with an IC50 of 1.2 ± 0.1 μM.


Effective magnetic fields for stationary light.
We describe a method to create effective gauge potentials for stationary-light polaritons. When stationary light is created in the interaction with a rotating ensemble of coherently driven double-Lambda type atoms, the equation of motion is that of a massive Schrödinger particle in a magnetic field. Since the effective interaction area for the polaritons can be made large, degenerate Landau levels can be created with degeneracy well above 100. This opens up the possibility to study the bosonic analogue of the fractional quantum Hall effect for interacting stationary-light polaritons.


Microvasculature Improvement of Heart in Diabetic Rat with Curcumin Supplementation.
To investigate the effect of curcumin supplementation on the improvement of heart microvasculature in Streptozotocin-induced diabetic rat. Streptozotocin (STZ: 60 mg/kg BW) was applied into rat to induce diabetic condition. Male rats were divided into three groups, control (C), diabetic (DM) and diabetic rats supplemented with curcumin (DMC) (200 mg/kg BW). After 8 and 12 weeks of experiments, heart microvasculature was investigated under vascular corrosion cast technique with scanning electron microscope (SEM). Destruction of heart microvasculature of DM group was observed at 8 and 12-week experiments. Five important categories of heart vessels and related veins and venules were examined respectively: right coronary arteries (RCA), medium arteries (MA), small arteries (SA), arterioles, and capillaries. RCA, cardiac arteries and veins demonstrated abnormality. Atypical patterns of vessels were presented, including shrinkage of artery vessels, capillary dropout, constriction and tortuousity of small cardiac vein and venules, and microaneurysm. At 12-week experiment, vascular lesion of DM group increased in complicated signs, including arterial constrictions and stenosis, arterial blind endings, capillary dropout and shrinkage. In addition, severity of microaneurysm dilatation of arterial branch of RCA, arterial tortuosity, coiled and twisting arteries were investigated. The diameters of vessels of all DM groups were evidently decreased. Subsequent to curcumin supplementation, typical and healthy heart microvasculatures were restored and redeveloped. The diameter sizes of DMC vessels have nearly increased back to normal situations, especially at artery, arteriole, and capillary levels. Efficiency of curcumin treatment beneficially repaired and recovered heart microvascular diabetic complications. This evidence suggests that potential anti-diabetic effect of curcumin is meaningful about the ongoing therapeutic consequences, owing to the improvement and recovery of heart blood vessels.


A Corpus Linguistics Approach to the Representation of Western Religious Beliefs in Ten Series of Chinese University English Language Teaching Textbooks.
The early Sino-Western contact was through the way in which religion and language interact to produce language contact. However, research on this contact is relatively limited to date, particularly in the realm of English language materials. In fact, there is a paucity of research on Western religions in English Language Teaching (ELT) textbooks. By applying corpus linguistics as a tool and the Critical Discourse Analysis as the theoretical framework, this manuscript critically investigates the significant semantic domains in ten English language textbook series that are officially approved and are widely used in Chinese universities. The findings suggest that various Western religious beliefs, which are the highly unusual topics in previous Chinese ELT textbooks, are represented in the textbook corpus. The results also show that when presenting the views and attitudes toward Western religious beliefs, these textbooks have adopted an eclectic approach to the material selection. Surprisingly, positive semantic prosody surrounding the concept of religion is evident and no consistent negative authorial stance toward religion is captured. Atheism has been assumed to be in the center of Chinese intellectual traditions and the essence of the Constitution of the Chinese Communist Party. Interestingly, the findings from this study provide a new understanding of Chinese foreign language textbooks in the new era, and its addition to the literature on the study of ELT textbooks, as well as its development worldwide.


Efficacy of combined therapy of periosteum and bone allograft in a critical-sized defect model in New Zealand white rabbits.
Large segmental bone defects caused by trauma, infection, or bone tumor resection are difficult to cure and have been a problem in the field of bone repair for decades. The objective of this study was to discuss the efficacy of combined therapy of free periosteum and bone allograft in treating bone defects and to provide a theoretical basis for clinical application of this therapy. A unilateral tibia cortical defect model in New Zealand white rabbits was established according to Girolamo method. Total 48 rabbits were randomized into 3 groups: a simple bone defect group (n=16), an autogenous bone graft group (n=16), and a periosteum and bone allograft combined therapy group (n=16). The efficacy was evaluated by imaging inspections and scoring, HE staining, and RT-PCR in postoperative weeks 2, 4, 8, and 12. The results of imaging and histopathological inspections in the study indicated that in postoperative weeks 4, 8, and 12 the experimental and control groups had statistically significant differences in Lane-Sandhu radiographic scoring and relative bone density when compared with the simple bone defect group (P<0.05). The RT-PCR results suggested that the expression of SPP-1, BMP-2, and VEGF in the experimental group was higher than in the control group (P<0.05) and the expression of Col Ia1 in the control group was higher than in the experimental group (P<0.05). Efficacies of the combined therapy (periosteum combined with bone allografting) and the criterion standard therapy (autogenous bone grafting) are equivalent in treating bone defects in New Zealand white rabbits.


1-(2-Fluoro-benz-yl)quinolinium bis-(2-sulfanylidene-1,3-dithiole-4,5-dithiol-ato-κS,S')nickelate(III).
The crystal structure of the title compound, (C(16)H(13)FN)[Ni(C(3)S(5))(2)], consists of Ni(III) complex anions and 1-(2-fluoro-benz-yl)quinolinium (fbq) cations. In the complex anion, the Ni(III) cation is chelated by two 2-sulfanylidene-1,3-dithiole-4,5-dithiol-ate (dmit) dianions in a distorted square-planar geometry; the two dmit mean planes are twisted with respect to each other at a dihedral angle of 8.44 (3)°. In the fbq cation, the dihedral angle between the benzene ring and the quinoline ring system is 80.57 (14)°. The centroid-centroid distance of 3.860 (5) Å between benzene rings indicates π-π stacking between adjacent fbq cations. The distance of 3.4958 (18) Å between the S atom and the centroid of the pyridine ring suggests the existence of a lone-pair-aromatic inter-action between the anion and the cation. A short S⋯S contact [3.387 (2) Å] is also observed in the crystal structure.


Substance P and the neurokinin-1 receptor in relation to eosinophilia in ulcerative colitis.
Substance P (SP) has been implicated in the pathophysiology of ulcerative colitis (UC) and it has been suggested that blocking of its effect would be advantageous in this disease. Eosinophils have also been implicated in the pathophysiology of UC. In the present study, specimens from the sigmoid colon of UC patients were investigated by the use of antisera against SP and the neurokinin-1 receptor (NK-1R) and staining for demonstration of eosinophils. The degrees of SP innervation and NK-1R immunoreaction, as well as the levels of eosinophil infiltration, varied between different patients. Interestingly, NK-1R immunoreaction in the epithelium was often seen to be the most marked where there were numerous eosinophils in the underlying mucosa and where the mucosa showed a marked morphologic derangement. The observations suggest that there are marked fluctuations in effects of SP and eosinophils during the disease. The infiltrating eosinophils may be involved in the destruction of the mucosal tissue. Furthermore, for the majority of cases where there is marked derangement of the mucosa, it is apparent that there is an upregulation of the NK-1 receptor in the epithelium in parallel with the infiltration of the eosinophils.


Is child maltreatment a leading cause of delinquency?
This article explores the assumption that child maltreatment is a major cause of juvenile delinquency. Although this relationship is widely accepted as fact, the research that exists in the literature so far is inconclusive at best, and at worst, deeply flawed. For too long, juvenile justice resources have been channeled into the apprehension and processing of youthful offenders, while relatively few dollars have gone into the research necessary to formulate a coherent strategy for solving the juvenile crime problem. Without funding for this much-needed research, the money we do spend on the control and prevention of juvenile crime is blindly spent.


Modelling the mass consumption potential of organic food: Evidence from an emerging economy.
The deterioration of the environment, shortage of resources, and frequent occurrence of food safety issues have made people increasingly concerned about themselves while maintaining their health and protecting the environment through food. Organic food, as a healthy and eco-friendly option, is gradually gaining attention. Based on the value-belief-norm theory, this study explores why individuals consume organic food and the range of factors that lead to this consumer behavior. This study adopted a cross-sectional design and collected quantitative data from conveniently selected 300 youth participants in Bangladesh using an online survey. The findings revealed that health values and motivation have a significant positive effect on healthy eating beliefs, which, together with the awareness of the consequences, affect personal norms toward organic food consumption. Personal norms also have a significant positive effect on organic food consumption behavior among Bangladeshi youth. Finally, trust on organic food positively moderates the effect of personal norms on organic food consumption. The findings of this study are expected to foster the development of a comprehensive framework to promote programs and policies focused on organic and healthy food consumption culture among youth in developing nations.


Inflammatory cytokines, growth factors, and depression.
There is a plausible role for cytokines, brain-derived neurotrophic factor (BDNF), and their interaction in major depressive disorder's (MDD) etiology. This review includes (i) briefly defining cytokines, (ii) a discussion of theories for why they may affect brain function, (iii) cross-sectional associations between cytokines and MDD, (iv) the effect of antidepressants on cytokines, (v) the behavioral effects of cytokines administration to humans, (vi) the behavior effects of their administration to animal models, and (vii) potential neurochemical systems influenced by cytokines. The role of BDNF is then briefly examined, along with a review of several studies that have examined a Val/Met polymorphism in the BDNF gene. The bidirectional relationship between BDNF and cytokines is subsequently discussed. Potential ramifications for MDD treatment that are appraised include (i) use of cytokine biomarkers for identifying specific populations for targeted MDD therapy, (ii) the use of medications that directly antagonize the role of inflammatory cytokines, (iii) potential indirect modifiers of cytokine activity, and (iv) possible downstream intracellular second messenger targets.


Transcranial magnetic stimulation-evoked EEG/cortical potentials in physiological and pathological aging.
The frontal cortex undergoes macrostructural and microstructural changes across the lifespan. These changes can be entirely physiological, such as the ones occurring in elderly individuals who are cognitively intact, or pathological, such as the ones occurring in patients with Alzheimer's disease. Here, we use simultaneous electroencephalography (EEG) and transcranial magnetic stimulation (TMS) to study how the excitability of the frontal cortex changes during healthy and pathological aging. Hence, we compared the TMS-evoked EEG potentials collected in healthy elderly individuals with the ones collected in healthy young individuals, and in patients with Alzheimer's disease. We have shown that the EEG response to TMS of the left superior frontal cortex is not affected by physiological aging but is markedly altered by cognitive impairment.


Recent Progress in External-Stimulus-Responsive 2D Covalent Organic Frameworks.
Recently, smart 2D covalent organic frameworks (COFs), combining the advantages of both inherent structure features and functional building blocks, have been demonstrated to show reversible changes in conformation, color, and luminescence in response to external stimuli. This review provides a summary on the recent progress of 2D COFs that are responsive to external stimuli such as metal ions, gas molecules, pH values, temperature, electricity, light, etc. Moreover, the responsive mechanisms and design strategies, along with the applications of these stimulus-responsive 2D COFs in chemical sensors and photoelectronic devices are also discussed. It is believed that this review would provide some guidelines for designing novel single-/multistimulus-responsive 2D COFs with controllable responsive behaviors for advanced photoelectronic applications.


Cortisol augments synthesis of growth hormone, but does not alter synthesis of prolactin and proopiomelanocortin, in the 120- to 125-day fetal ovine pituitary.
In adult animal pituitaries or in cultured pituitary tumor cells, glucocorticoids are regulators of GH, PRL, and proopiomelancortin (POMC) synthesis. However, ovine fetal plasma cortisol concentrations are low until shortly before parturition, suggesting that cortisol may not normally regulate hormone synthesis in the fetal pituitary. To investigate whether cortisol could affect fetal synthesis of GH, PRL, and POMC, we obtained fetal pituitary tissue from normal fetuses and from fetuses which had received cortisol infusion for 48 h. Tissues were labeled in short term organ culture and the newly synthesized proteins were displayed by two-dimensional gel electrophoresis and autoradiography. Results were quantified by computerized integration of the area and density of the autoradiographic spots after high resolution television scanning. Cortisol infusion augmented synthesis of GH in comparison to controls (P = 0.01), but did not alter PRL synthesis. Cortisol also did not inhibit POMC synthesis in either the anterior pituitary or the neurointermediate lobe. These data suggest that the pituitary-adrenocortical slow feedback inhibition of POMC synthesis is not functional in the ovine fetus at 120 to 125-days gestation, but that pituitary somatotropes are responsive to glucocorticoids at this stage of fetal development.


Regulation of the expression of the phosphoenolpyruvate carboxykinase gene in cultured rat hepatocytes by glucagon and insulin.
The induction of phosphoenolpyruvate carboxykinase (PEPCK) by glucagon was studied in primary rat hepatocyte cultures by determining the time course of the sequential events, increases in the enzyme's mRNA abundance, synthesis rate, amount and activity, and by investigating the antagonistic action of insulin on the induction by glucagon. 1. The mRNA of PEPCK was induced maximally 2-3 h after addition of 10 nM glucagon, as detected by Northern-blot analysis after hybridization with a biotinylated antisense RNA of PEPCK. 2. The synthesis rate of PEPCK increased maximally 2-3 h after application of glucagon as revealed by pansorbin-linked immunoprecipitation of [35S]methionine-labelled PEPCK. 3. The enzyme amount and activity was maximally induced 4 h after glucagon application. 4. The mRNA of PEPCK was half-maximally induced by 0.1 nM and maximally by 1 nM and 10 nM glucagon. The half-maximal induction by 0.1 nM glucagon was antagonized almost totally, and the maximal induction by 1 nM glucagon partially, while the maximal induction by 10 nM glucagon remained unaffected by 10 nM insulin. The results show that in cultured rat hepatocytes physiological concentrations of glucagon stimulated the induction of PEPCK by an increase in mRNA, that the glucagon-dependent increase in mRNA and enzyme-synthesis rate occurred in parallel and preceded the increase of enzyme amount and activity by 1-1.5 h, and that physiological levels of insulin antagonized the induction by glucagon in the physiological concentration range, with glucagon being the dominant hormone.


Advancements and Applications of Liquid Biopsies in Oncology: A Narrative Review.
According to the World Health Organization (WHO), nearly 10 million people died from cancer worldwide in 2020, making it the leading cause of mortality. Liquid biopsies, which provide non-invasive and real-time monitoring of tumor dynamics, have evolved into innovative diagnostic techniques in the field of oncology. Liquid biopsies offer important insights into tumor heterogeneity, treatment response, minimum residual disease identification, and personalized treatment of cancer through the analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), extracellular vesicles, and microRNAs. They offer several advantages over traditional tissue biopsies, such as being less invasive, more convenient, more representative of tumor heterogeneity and dynamics, and more informative for guiding personalized treatment decisions. Liquid biopsies are being utilized increasingly in clinical oncology, particularly for patients with metastatic disease who require ongoing monitoring and treatment modification. In this narrative review article, we review the latest developments of liquid biopsy technologies, their applications and limitations, and their potential to transform diagnosis, prognosis, and management of cancer patients.


Is leaf area of Norway spruce (Picea abies L. Karst.) and European larch (Larix decidua Mill.) affected by mixture proportion and stand density?
Trees with otherwise equal dimensions have different leaf areas if they are located in different stand types. While leaf area of European larch is affected by mixture proportion, leaf area of Norway spruce is affected by stand density. Leaf area is a key parameter for evaluating growth efficiency of trees, and therefore needs to be measured as consistently and accurately as possible. This is even more important when comparing monospecific and mixed stands. The aim of the study is to find combinations of parameters and allometric relationships that can be used to estimate accurately the leaf area of individual trees. Allometries of the measured leaf area of 194 trees in 12 stands were analysed in order to find variables affecting leaf area. Existing functions from the literature were validated. Finally, models were fitted to find the most appropriate method for estimating leaf area of mixed and monospecific stands of Norway spruce and European larch. Allometric relationships of leaf area to other measurable characteristics of trees vary in different stand types. Besides individual tree dimensions such as diameter and crown surface area, leaf area of Norway spruce is related to stand density, whereas the leaf area of European larch is dependent on the admixture of Norway spruce in the stand. In contrast to models for estimating individual tree leaf area of Norway spruce, models for leaf area of European larch have to consider mixture proportions in order to correctly interpret the growth efficiency of mixed stands.


Psychiatric disorders and traumatic brain injury.
Psychiatric disorders after traumatic brain injury (TBI) are frequent. Researches in this area are important for the patients' care and they may provide hints for the comprehension of primary psychiatric disorders. Here we approach epidemiology, diagnosis, associated factors and treatment of the main psychiatric disorders after TBI. Finally, the present situation of the knowledge in this field is discussed.


SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FEATURES OF VITREORETINAL LYMPHOMA IN 55 EYES.
To evaluate spectral domain optical coherence tomography (SD-OCT) features of vitreoretinal lymphoma (VRL). Review of records and SD-OCT images of vitreoretinal lymphoma evaluated at Ocular Oncology Service, Wills Eye Hospital between July 1, 2000, and April 1, 2019. There were 55 eyes of 32 patients included. At presentation, SD-OCT features included vitreous opacities (n = 36, 65%), preretinal deposits (n = 7, 13%), intraretinal deposits (n = 8, 15%), subretinal deposits (n = 20, 36%), retinal pigment epithelium abnormalities (n = 35, 64%), and subretinal pigment epithelium deposits (n = 35, 64%). Of 36 eyes with observed tumor progression, comparison (initial visit vs. time of progression) revealed more intraretinal deposits (17% vs. 50%, P = 0.005) at progression. Of 15 eyes with tumor recurrence, comparison (initial visit vs. time of recurrence) revealed more intraretinal deposits (7% vs. 47%, P = 0.04) at recurrence. At last visit, 39 eyes demonstrated tumor regression. By comparison (initial presentation vs. regression), there were less frequent vitreous opacities (67% vs. 0%, P < 0.001), intraretinal deposits (15% vs. 0%, P = 0.03), subretinal deposits (36% vs. 0%, P < 0.001), and subretinal pigment epithelium deposits (69% vs. 21%, P < 0.001) at regression. Using SD-OCT in patients with vitreoretinal lymphoma, local tumor regression correlated with a reduction in vitreous opacities, intraretinal deposits, subretinal deposits, and subretinal pigment epithelium deposits. SD-OCT is useful in judging vitreoretinal lymphoma response to therapy.


Relationship between histology, development and tumorigenesis of mammary gland in female rat.
The mammary gland is a dynamic organ that undergoes structural and functional changes associated with growth, reproduction, and post-menopausal regression. The postnatal transformations of the epithelium and stromal cells of the mammary gland may contribute to its susceptibility to carcinogenesis. The increased cancer incidence in mammary glands of humans and similarly of rodents in association with their development is believed to be partly explained by proliferative activity together with lesser degree of differentiation, but it is not completely understood how the virgin gland retains its higher susceptibility to carcinogenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer. An early first full-term pregnancy may have a protective effect. Rodent models are useful for investigating potential breast carcinogens. The purpose of this review is to help recognizing histological appearance of the epithelium and the stroma of the normal mammary gland in rats, and throughout its development in relation to tumorigenic potential.


Three-dimensional cartilage tissue engineering using adult stem cells from osteoarthritis patients.
To determine whether it is possible to engineer 3-dimensional hyaline cartilage using mesenchymal stem cells derived from the bone marrow (BMSCs) of patients with osteoarthritis (OA). Expanded BMSCs derived from patients with hip OA were seeded onto polyglycolic acid scaffolds and differentiated using transforming growth factor beta3 in the presence or absence of parathyroid hormone-related protein (PTHrP) to regulate hypertrophy. Micromass pellet cultures were established using the same cells for comparison. At the end of culture, the constructs or pellets were processed for messenger RNA (mRNA) analysis by quantitative real-time reverse transcription-polymerase chain reaction. Matrix proteins were analyzed using specific assays. Cartilage constructs engineered from BMSCs were at least 5 times the weight of equivalent pellet cultures. Histologic, mRNA, and biochemical analyses of the constructs showed extensive synthesis of proteoglycan and type II collagen but only low levels of type I collagen. The protein content was almost identical to that of cartilage engineered from bovine nasal chondrocytes. Analysis of type X collagen mRNA revealed a high level of mRNA in chondrogenic constructs compared with that in undifferentiated BMSCs, indicating an increased risk of hypertrophy in the tissue-engineered cells. However, the inclusion of PTHrP at a dose of 1 microM or 10 microM during the culture period resulted in significant suppression of type X collagen mRNA expression and a significant decrease in alkaline phosphatase activity, without any loss of the cartilage-specific matrix proteins. Three-dimensional hyaline cartilage can be engineered using BMSCs from patients with OA. This method could thus be used for the repair of cartilage lesions.


Paradoxical Anticonvulsant Effect of Cefepime in the Pentylenetetrazole Model of Seizures in Rats.
Many β-lactam antibiotics, including cephalosporins, may cause neurotoxic and proconvulsant effects. The main molecular mechanism of such effects is considered to be γ-aminobutyric acid type a (GABAa) receptor blockade, leading to the suppression of GABAergic inhibition and subsequent overexcitation. We found that cefepime (CFP), a cephalosporin, has a pronounced antiepileptic effect in the pentylenetetrazole (PTZ)-induced seizure model by decreasing the duration and severity of the seizure and animal mortality. This effect was specific to the PTZ model. In line with findings of previous studies, CFP exhibited a proconvulsant effect in other models, including the maximal electroshock model and 4-aminopyridine model of epileptiform activity, in vitro. To determine the antiepileptic mechanism of CFP in the PTZ model, we used whole-cell patch-clamp recordings. We demonstrated that CFP or PTZ decreased the amplitude of GABAa receptor-mediated postsynaptic currents. PTZ also decreased the current decay time constant and temporal summation of synaptic responses. In contrast, CFP slightly increased the decay time constant and did not affect summation. When applied together, CFP prevented alterations to the summation of responses by PTZ, strongly reducing the effects of PTZ on repetitive inhibitory synaptic transmission. The latter may explain the antiepileptic effect of CFP in the PTZ model.


[Non cholangio-contrast cholangiopancreatography using multi-slice spiral CT].
To investigate the feasibility of multi-slice spiral CT (MSCT) for cholangiopancreatography without cholangio-contrast. Ten patients without any digestion system diseases and 24 patients with suspected pancreatic malignancy received the 16-slice spiral CT multi-phased contrast-enhanced scanning. The images of patients without any digestion system diseases and cancer-suffered patients were curved reformatted (CR) technique to perform the structure of pancreatic duct, common bile duct, and ampulla. The cholangiopancreatical systems of the cancer suffered patient were reconstructed through volume rendering technique (VRT), minimum intensity projection (MinIP), and indirect minimum intensity projection (IMinIP). The results of patients without any digestion system diseases in curved multiplanar reconstruction were analyzed; meanwhile display rates of the pancreatic duct, common bile duct, and ampulla were evaluated. of the four different cholangiopancreatographies were compared. The display rate of pancreatic duct in the CR images was 90.0 (9/10) with an average diameter of (2.63 +/- 0.51) mm. Sub-pancreatic duct could be seen in 88.9% (8/9) of them. The display rate of common bile duct in the CR images was 100% (10/10) with an average diameter of (7.45 +/- 1.12) mm. The display rate of ampulla was 60.0 (6/10), which was affected by the filling status of duodenum. The cholangiopancreatography using CR, VRT, MinIP, and IMinIP for patients with pancreatic cancer reveal the whole pancreatic and common bile duct, and the modality of distal obstructed bile duct. The result showed that IminIP got the best outcome (98.6%), while VRT got the worst (68.1%). The negative CT cholangiopancreatography is a simple and non-invasive examination. It reflects both the 3-dimensional cholangio-pancreatic anatomical structure and its adjacent condition. It has curtain clinical application values, especially for patients with obstructed duct system.


Increased Histone Deacetylase Activity Involved in the Suppressed Invasion of Cancer Cells Survived from ALA-Mediated Photodynamic Treatment.
Previously, we have found that cancer cells survived from 5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) have abnormal mitochondrial function and suppressed cellular invasiveness. Here we report that both the mRNA expression level and enzymatic activity of histone deacetylase (HDAC) were elevated in the PDT-derived variants with dysfunctional mitochondria. The activated HDAC deacetylated histone H3 and further resulted in the reduced migration and invasion, which correlated with the reduced expression of the invasion-related genes, matrix metalloproteinase 9 (MMP9), paternally expressed gene 1 (PEG1), and miR-355, the intronic miRNA. Using chromatin immunoprecipitation, we further demonstrate the reduced amount of acetylated histone H3 on the promoter regions of MMP9 and PEG1, supporting the down-regulation of these two genes in PDT-derived variants. These results indicate that HDAC activation induced by mitochondrial dysfunction could modulate the cellular invasiveness and its related gene expression. This argument was further verified in the 51-10 cybrid cells with the 4977 bp mtDNA deletion and A375 ρ⁰ cells with depleted mitochondria. These results indicate that mitochondrial dysfunction might suppress tumor invasion through modulating histone acetylation.


Designing a comprehensive minimum dataset for patients with COVID-19 in Iranian hospital information systems.
The Minimum Data Set (MDS) plays a vital role in data exchange, collection and quality improvement. In the context of the COVID-19 pandemic, there is a need for a tailored MDS that aligns with the specific information needs of the Iranian community and integrates seamlessly into the country's Hospital Information Systems (HIS). The study aimed to develop a comprehensive MDS for COVID-19 patients in Iran, with objectives to identify essential data elements and integrate the MDS into HIS, enhancing data exchange and supporting decision-making. This study employed a comparative-descriptive approach to design COVID-19 patient data elements based on World Health Organisation and Centers for Disease Control and Prevention guidelines. The Delphi technique involved 35 experts in two rounds for checklist refinement. The finalised MDS consisted of 9 main terms and 80 sub-terms, analysed using descriptive statistics and IBM SPSS software. Of 35 experts involved with the study, 69% were male and 31% female, and Health Information Management experts were the majority (34%). The refined MDS for COVID-19 in Iran comprises 50 data elements, while 30 elements were excluded. The MDS includes 8 main terms and 80 sub-terms, with unanimous approval for identity, underlying disease, and treatment sections. The customised MDS for COVID-19 patients in Iran addresses data collection challenges and supports effective disease prevention and management. By providing comprehensive and reliable information, the MDS enhances healthcare quality, facilitates timely access to medical records, and fosters integrated health services.


Electric Control of Helicity-Dependent Photocurrent and Surface Polarity Detection on Two-Dimensional Bi2O2Se Nanosheets.
Bismuth oxyselenide (Bi2O2Se) is a two-dimensional (2D) layered semiconductor material with high electron Hall mobility and excellent environmental stability as well as strong spin-orbit interaction (SOI), which has attracted intense attention for application in spintronic and spin optoelectronic devices. However, a comprehensive study of spin photocurrent and its microscopic origin in Bi2O2Se is still missing. Here, the helicity-dependent photocurrent (HDPC) was investigated in Bi2O2Se nanosheets. By analyzing the dependence of HDPC on the angle of incidence, we find that the HDPC originates from surface states with Cs symmetry in Bi2O2Se, which can be attributed to the circular photogalvanic effect (CPGE) and circular photon drag effect (CPDE). It is revealed that the HDPC current almost changes linearly with the source-drain voltage. Furthermore, we demonstrate effective tuning of HDPC in Bi2O2Se by ionic liquid gating, indicating that the spin splitting of the surface electronic structure is effectively tuned. By analyzing the gate voltage dependence of HDPC, we can unambiguously identify the surface polarity and the surface electronic structure of Bi2O2Se. The large HDPC in Bi2O2Se nanosheets and its efficient electrical tuning demonstrate that 2D Bi2O2Se nanosheets may provide a good platform for opto-spintronics devices.


Experimental study and numerical simulation of the kinetic energy recovery of the mine's exhaust gas.
In mines, the exhaust gas is mainly discharged from main ventilators in free dissipation state. The effective recovery of its kinetic energy is lucrative from economical and technical standpoints. This study is focused on recovering the kinetic energy of the exhaust gas without deteriorating the main ventilator's safe operation or increasing power dissipation. The related experiments and numerical simulations were performed for the conical diffusers with diffusing angles of 16° and inlet diameters of 220 and 320 mm, respectively. By examining the start-up and operation states of the wind turbines using inlet collectors with conical, circular arc, and cone-arc shapes, it was found that the wind speed at the inlet of the drainage tube exceeded 4 and 20 m/s at the minimal and maximal distances from the wind turbine, respectively. The wind speed at the overflow tube outlet was no less than 1.8 m/s, proving a certain recovery of kinetic energy by the wind turbine. Thus, the critical distance between the diffuser and the inlet collector should be at least four times the diffuser's inlet diameter. Finally, the velocity, pressure, and flow fields in the vortex core regions of the kinetic recovery system with different types of inlet collectors were simulated with the FLUENT commercial software package. The simulation results revealed that the circular-arc collector outperformed other three tested configurations in kinetic energy recovery.Implications: This study is focused on recovering the kinetic energy of the exhaust gas without deteriorating the main ventilator's safe operation or increasing power dissipation. China is a country with coal as its main energy source, which releases over ten billion cubic meters of the exhaust gas annually. In addition to low-concentration methane, there is also the exhaust gas released at a velocity of about 20 m/s, which kinetic energy recovery would be very lucrative.The significance of this study is that the mine's main ventilator outlet was simplified as two conical diffusers with parameters α=16°/n=2 and α=16°/n=2.5, and the optimal critical distance between the diffuser and the collector was determined as 4Di, where Di was the diffuser's inlet diameter. Under that optimal condition, the system can achieve the maximum power without affecting the ventilator's normal operation. It is instructive to make full use of and manage the exhaust gas in mine that fits the journal on the purpose of air waste management.Finally, we provide a statement serious that the article is original and unpublished and is not being considered for publication elsewhere.


Spontaneous imbibition experiment in newspaper sheets.
We study the behavior of an ink-paper interface in a spontaneous imbibition experiment as a function of time and paper orientation. To characterize the interface roughness the growth beta and Hurst H exponents (calculated using the root mean square interface width W) and the H{q} scaling exponent (calculated using the qth order height-height correlation function) are used. Our results indicate that the values of H and H{q} depend on the orientation of the paper sheets, while beta does not, and that the interface exhibits a multiaffine character during all its evolution.


Extraordinary magnetic field enhancement with metallic nanowire: role of surface impedance in Babinet's principle for sub-skin-depth regime.
We propose and analyze the "complementary" structure of a metallic nanogap, namely, the metallic nanowire for magnetic field enhancement. A huge enhancement of the field up to a factor of 300 was achieved. Introducing the surface impedance concept, we also develop and numerically confirm a new analytic theory which successfully predicts the field enhancement factors for metal nanostructures. Compared to the predictions of the classical Babinet principle applied to a nanogap, an order of magnitude difference in the field enhancement factor was observed for the sub-skin-depth regime nanowire.


Neurons and astrocytes in an infantile neuroaxonal dystrophy (INAD) mouse model show characteristic alterations in glutamate-induced Ca2+ signaling.
INAD (infantile neuroaxonal dystrophy, OMIM#256600), an autosomal recessive inherited degenerative disease, is associated with PLA2G6 mutations. PLA2G6 encodes Ca2+-independent phospholipase A2 (VIA iPLA2). However, it is unclear how the PLA2G6-mutations lead to disease. Non-canonical functions, which were suggested for VIA iPLA2, such as regulation of cellular and mitochondrial Ca2+ are promising candidates. Therefore, we investigate glutamate (Glu)-evoked Ca2+ signals in neurons and astrocytes in co-culture obtained from three INAD mouse model strains with Pla2g6 mutations, (i) hypomorphic Pla2g6 allele with reduced transcript levels, (ii) knocked-out Pla2g6, and (iii) (G373R)-point mutation with inactive VIA iPLA2 enzyme. Homozygous offspring from these strains develop pathology similar to that observed in INAD patients. We found that in mouse neurons the Pla2g6 mutation disrupted the dependency of Glu-induced extracellular Ca2+ influx on mitochondrial Ca2+ uptake. Thus, in neurons with Pla2g6 mutation we did not detect the characteristic reduction in Glu-induced Ca2+ influx upon treatment with Ru360, a blocker of mitochondrial Ca2+ uniporter, or with rotenone. In contrast to neurons, in astrocytes, both with Pla2g6 mutation or wild-type cells, the treatment with Ru360 or rotenone reduced the rate of Glu-induced Ca2+ influx ∼2-fold. This Ca2+ influx in astrocytes represents capacitative Ca2+ entry. In astrocytes with Pla2g6 mutation, the Glu-induced Ca2+ influx was ∼2-fold lower than in wild-type controls. We suggest that this is the mechanism for strongly decreased durations of Glu-induced Ca2+ responses in astrocytes with Pla2g6 mutation. We could mimic the mutation by pharmacological inhibition of iPLA2 using S-BEL. Thus, lack of VIA iPLA2 activity caused effects in astrocytes. In summary, three INAD mouse models show comparable changes in Glu-induced Ca2+ signaling, but specific for neurons or astrocytes. This finding helps to identify pathways altered during INAD and highlights non-canonical VIA iPLA2 functions, like regulation of cellular Ca2+ fluxes by mitochondria or capacitative Ca2+-entry.


Oocyte donation and endometriosis: What are the lessons?
Outcomes of in vitro fertilization cycles in women with endometriosis are significantly worse than in patients without this condition. The impact of endometriosis on ovarian reserve and the quality of retrieved oocytes seems evident. Lower implantation rates, however, raise the question whether this finding is purely the consequence of lower number and poorer quality of embryos, or whether it also reflects compromised endometrial receptivity. Oocyte donation provides an interesting model to investigate reproductive outcome because factors affecting the oocytes are excluded, especially if cycles using oocytes derived from the same donor are analyzed. These studies have shown lower implantation rates in nonendometriotic patients who received oocytes from women with endometriosis, whereas healthy donated oocytes have proven to contribute to a pregnancy with similar chances in women without the disease. The question still to be answered is whether this situation applies for natural cycles or whether it is the use of gonadotropin-releasing hormone analogs and hormonal replacement therapy used for endometrial priming in oocyte recipients that reestablishes an adequate uterine environment. Using a genomic tool based on microarray technology (endometrial receptivity array), the study of differential gene expression in the eutopic endometrium of endometriosis patients undergoing oocyte donation treatment is still underway.


Bowen-Conradi syndrome in non Hutterite infant.
The authors' review their experience of Bowen-Conradi syndrome and the available literature. They point out that there have been three previously published reports of possible Bowen-Conradi syndrome in non Hutterite children.


Implementing brief Dynamic Interpersonal Therapy (DIT) in a VA Medical Center.
Background: Given increasing mental health needs in the VA, identifying strategies to deliver new services is critical.Aims: This paper describes the process of navigating provider, patient and systems barriers of an initiative to increase choice, access and quality of psychotherapy at the VA by incorporating an evidence-based short-term, psychodynamic psychotherapy.Methods: Brief Dynamic Interpersonal Therapy (DIT) was selected as a viable model for implementation. Data were gathered on the process of implementation, barriers, Veterans seen, and access to psychodynamic psychotherapy.Results: Nine psychologists and 22 masters level pre-doctoral psychology externs have delivered DIT to 73 Veterans. Veterans referred for psychodynamic psychotherapy annually increased 360%. Furthermore, DIT has become the dominant form of psychodynamic psychotherapy requested of the psychology service representing 70.1% of psychodynamic psychotherapy referrals. Strategies are presented for addressing: (1) provider ability, flexibility and motivation, (2) Veteran perception of relevance, distinctiveness and adaptability to complex presenting issues and (3) administrative support.Conclusions: Implementing an evidence-based short-term psychodynamic treatment option in the VA is feasible. VA mental health providers can be trained in brief psychodynamic psychotherapy and can successfully implement those approaches in VA settings. Finally, psychodynamic treatment approaches may serve as a promising alternative to currently available treatments.


Evidence for global motion interactions between first-order and second-order stimuli.
Recent research indicates that the early stages of visual-motion analysis involve two parallel neural pathways, one conveying information from luminance-defined (first-order) image features, the other conveying information from texture-defined (second-order) features. It is still not clear whether these two pathways converge during later stages of global motion integration. According to one account they remain segregated, and feed separate global analyses. In the alternative account, all responses feed a common stage of global analysis. Two perceptual phenomena are universally held to result from interactions between detector responses during global motion integration--direction repulsion and motion capture. We conducted two psychophysical experiments on these phenomena to test for segregation of first-order and second-order responses during integration. Stimuli contained two components, either two random-block patterns transparently drifting in different directions (repulsion measurements), or a drifting square-wave grating superimposed on an incoherent random-block pattern (capture measurements). Repulsion and capture effects were measured when both stimulus components were the same order, and when one component was first order and the other was second order. Both effects were obtained for all combinations of first-order and second-order patterns. Repulsion effects were stronger with first-order inducing patterns, and capture effects were stronger with second-order inducers. The presence of perceptual interactions regardless of stimulus order strongly suggests that responses in first-order and second-order pathways interact during global motion analysis.


Anatomical and Biomechanical Properties of the Junction between Stem and Aerial Roots of Selenicereus undatus.
Cacti have a distinct adaptation to arid conditions with a massive water storing tissue surrounding a weak central woody cylinder. However, they have not been studied as extensively as other plants have been. Selenicereus undatus is a hemi-epiphytic root climber that attaches itself to supporting plants or rocks with adventitious roots. The anatomy and biomechanics of the adventitious roots were studied using light microscopy, X-ray tomography and pullout and uniaxial tensile tests. The central cylinder of the roots is highly lignified and is connected to the vascular system of the shoot in a peculiar way. Xylem elements of the root turn 90 degrees towards the base of the shoot and merge laterally and below the junction with those from the shoot. Tensile and pull-out tests showed that failure occurs either at the root or junction, with the fracture surface mainly comprising the area where xylem elements from the root merge with those from the shoot. However, damage to the cortical tissue was minimal, and the measured forces showed that adventitious roots have a high safety factor. Even a complete failure of the junction after pullout does not result in severe injury to the cortex, which could lead to water loss or the entry of pathogens.


Syp1 regulates the clathrin-mediated and clathrin-independent endocytosis of multiple cargo proteins through a novel sorting motif.
Internalization of proteins from the plasma membrane (PM) allows for cell-surface composition regulation, signaling of network modulation, and nutrient uptake. Clathrin-mediated endocytosis (CME) is a major internalization route for PM proteins. During CME, endocytic adaptor proteins bind cargoes at the cell surface and link them to the PM and clathrin coat. Muniscins are a conserved family of endocytic adaptors, including Syp1 in budding yeast and its mammalian orthologue, FCHo1. These adaptors bind cargo via a C-terminal μ-homology domain (μHD); however, few cargoes exhibiting muniscin-dependent endocytosis have been identified, and the sorting sequence recognized by the µHD is unknown. To reveal Syp1 cargo-sorting motifs, we performed a phage display screen and used biochemical methods to demonstrate that the Syp1 µHD binds DxY motifs in the previously identified Syp1 cargo Mid2 and the v-SNARE Snc1. We also executed an unbiased visual screen, which identified the peptide transporter Ptr2 and the ammonium permease Mep3 as Syp1 cargoes containing DxY motifs. Finally, we determined that, in addition to regulating cargo entry through CME, Syp1 can promote internalization of Ptr2 through a recently identified clathrin-independent endocytic pathway that requires the Rho1 GTPase. These findings elucidate the mechanism of Syp1 cargo recognition and its role in trafficking.


An innovative design for cardiopulmonary resuscitation manikins based on a human-like thorax and embedded flow sensors.
Cardiopulmonary resuscitation manikins are used for training personnel in performing cardiopulmonary resuscitation. State-of-the-art cardiopulmonary resuscitation manikins are still anatomically and physiologically low-fidelity designs. The aim of this research was to design a manikin that offers high anatomical and physiological fidelity and has a cardiac and respiratory system along with integrated flow sensors to monitor cardiac output and air displacement in response to cardiopulmonary resuscitation. This manikin was designed in accordance with anatomical dimensions using a polyoxymethylene rib cage connected to a vertebral column from an anatomical female model. The respiratory system was composed of silicon-coated memory foam mimicking lungs, a polyvinylchloride bronchus and a latex trachea. The cardiovascular system was composed of two sets of latex tubing representing the pulmonary and aortic arteries which were connected to latex balloons mimicking the ventricles and lumped abdominal volumes, respectively. These balloons were filled with Life/form simulation blood and placed inside polyether foam. The respiratory and cardiovascular systems were equipped with flow sensors to gather data in response to chest compressions. Three non-medical professionals performed chest compressions on this manikin yielding data corresponding to force-displacement while the flow sensors provided feedback. The force-displacement tests on this manikin show a desirable nonlinear behaviour mimicking chest compressions during cardiopulmonary resuscitation in humans. In addition, the flow sensors provide valuable data on the internal effects of cardiopulmonary resuscitation. In conclusion, scientifically designed and anatomically high-fidelity designs of cardiopulmonary resuscitation manikins that embed flow sensors can improve physiological fidelity and provide useful feedback data.


The LLNA: A Brief Review of Recent Advances and Limitations.
Allergic contact dermatitis is the second most commonly reported occupational illness, accounting for 10% to 15% of all occupational diseases. This highlights the importance of developing rapid and sensitive methods for hazard identification of chemical sensitizers. The murine local lymph node assay (LLNA) was developed and validated for the identification of low molecular weight sensitizing chemicals. It provides several benefits over other tests for sensitization because it provides a quantitative endpoint, dose-responsive data, and allows for prediction of potency. However, there are also several concerns with this assay including: levels of false positive responses, variability due to vehicle, and predictivity. This report serves as a concise review which briefly summarizes the progress, advances and limitations of the assay over the last decade.


Structures of the Catalytic Domain of Bacterial Primase DnaG in Complexes with DNA Provide Insight into Key Priming Events.
Bacterial primase DnaG is an essential nucleic acid polymerase that generates primers for replication of chromosomal DNA. The mechanism of DnaG remains unclear due to the paucity of structural information on DnaG in complexes with other replisome components. Here we report the first crystal structures of noncovalent DnaG-DNA complexes, obtained with the RNA polymerase domain of Mycobacterium tuberculosis DnaG and various DNA ligands. One structure, obtained with ds DNA, reveals interactions with DnaG as it slides on ds DNA and suggests how DnaG binds template for primer synthesis. In another structure, DNA in the active site of DnaG mimics the primer, providing insight into mechanisms for the nucleotide transfer and DNA translocation. In conjunction with the recent cryo-EM structure of the bacteriophage T7 replisome, this study yields a model for primer elongation and hand-off to DNA polymerase.


Simple proxies of insulin resistance identify obese metabolic dysfunction-associated fatty liver disease subjects with advanced liver disease.
Insulin resistance (IR) plays a pivotal role in the pathogenesis of Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD), which can progress to liver fibrosis. We examined the relationship of different IR scores with markers of MAFLD severity in obese individuals. In this retrospective observational study, 346 non-diabetic, overweight/obese individuals with newly diagnosed MAFLD (age 50.2 ± 13.3 years, 34% females, BMI 30.8 ± 4.4 kg/m2 ) underwent liver stiffness (LS) and controlled attenuation parameter (CAP) measurements by Fibroscan® to assess liver fibrosis and steatosis. Biochemical data were collected to calculate surrogate markers of IR (Homoeostasis model assessment - insulin resistance index [HOMA-IR], triglyceride-glucose index, triglyceride by HDL ratio), liver fibrosis (Nonalcoholic Fatty Liver Diseases fibrosis score, fibrosis-4 score, Aspartate aminotransferase to platelet ratio index) and steatosis (fatty liver index, hepatic steatosis index). All three IR scores were associated with CAP, while only HOMA-IR positively correlated with LS (r = 0.275, p < 0.0001), independent of age and sex, BMI, transaminases, and fibrosis markers. Insulin-resistant individuals (HOMA-IR >2.5, n = 165) had higher liver enzymes, CAP and LS, with a 4-fold increased risk of severe liver disease (LS >9.7 kPa, OR 4.42[1.95-10.01], p = 0.0002). Among HOMA-IR components, fasting plasma insulin (FPI) was independently associated with LS (r = 0.270, p < 0.0001). ROC AUC for HOMA-IR and FPI to predict severe liver disease were virtually identical (0.748 and 0.758, respectively). HOMA-IR is independently associated with non-invasive markers of MAFLD severity in overweight/obese individuals. This relationship is largely mediated by hyperinsulinemia, regardless of BMI. Measuring insulin levels in MAFLD individuals might be useful to identify those at risk of liver fibrosis.


Unraveling the epigenetic landscape of pulmonary arterial hypertension: implications for personalized medicine development.
Pulmonary arterial hypertension (PAH) is a multifactorial disease associated with the remodeling of pulmonary blood vessels. If left unaddressed, PAH can lead to right heart failure and even death. Multiple biological processes, such as smooth muscle proliferation, endothelial dysfunction, inflammation, and resistance to apoptosis, are associated with PAH. Increasing evidence suggests that epigenetic factors play an important role in PAH by regulating the chromatin structure and altering the expression of critical genes. For example, aberrant DNA methylation and histone modifications such as histone acetylation and methylation have been observed in patients with PAH and are linked to vascular remodeling and pulmonary vascular dysfunction. In this review article, we provide a comprehensive overview of the role of key epigenetic targets in PAH pathogenesis, including DNA methyltransferase (DNMT), ten-eleven translocation enzymes (TET), switch-independent 3A (SIN3A), enhancer of zeste homolog 2 (EZH2), histone deacetylase (HDAC), and bromodomain-containing protein 4 (BRD4). Finally, we discuss the potential of multi-omics integration to better understand the molecular signature and profile of PAH patients and how this approach can help identify personalized treatment approaches.


A SAM-key domain required for enzymatic activity of the Fun30 nucleosome remodeler.
Fun30 is the prototype of the Fun30-SMARCAD1-ETL subfamily of nucleosome remodelers involved in DNA repair and gene silencing. These proteins appear to act as single-subunit nucleosome remodelers, but their molecular mechanisms are, at this point, poorly understood. Using multiple sequence alignment and structure prediction, we identify an evolutionarily conserved domain that is modeled to contain a SAM-like fold with one long, protruding helix, which we term SAM-key. Deletion of the SAM-key within budding yeast Fun30 leads to a defect in DNA repair and gene silencing similar to that of the fun30Δ mutant. In vitro, Fun30 protein lacking the SAM-key is able to bind nucleosomes but is deficient in DNA-stimulated ATPase activity and nucleosome sliding and eviction. A structural model based on AlphaFold2 prediction and verified by crosslinking-MS indicates an interaction of the long SAM-key helix with protrusion I, a subdomain located between the two ATPase lobes that is critical for control of enzymatic activity. Mutation of the interaction interface phenocopies the domain deletion with a lack of DNA-stimulated ATPase activation and a nucleosome-remodeling defect, thereby confirming a role of the SAM-key helix in regulating ATPase activity. Our data thereby demonstrate a central role of the SAM-key domain in mediating the activation of Fun30 catalytic activity, thus highlighting the importance of allosteric activation for this class of enzymes.


Nd:YAG laser influence on microtensile bond strength of different adhesive systems for human dentin.
The purpose of this study was to investigate the influence of Nd:YAG on microtensile bond strength (microTBS) of different adhesive systems for human dentin. Lasers have been widely used in dentistry. New adhesive systems with different chemical compositions are introduced every year, and it is important to investigate the bonding of new adhesive systems to dentin irradiated with laser. The occlusal surfaces of third molars were removed to obtain flat dentin surfaces. The teeth were randomly divided into six groups. Each adhesive system was applied, according to manufacturers' instructions, to surface dentine with and without Nd:YAG laser irradiation (0.9 W, 15 Hz, 60 mJ per pulse). A block of composite resin was built over the adhesive layer. The specimens were sectioned to obtain 0.70 x 0.70 mm of transversal section. Twenty test specimens were selected for each group, and were then submitted to microTBS on a universal testing machine. According to Student's t-test, for Single Bond, there was no statistically significant difference without (49.32 MPa) and with (47.34 MPa) laser application (p = 0.60). For the Tyrian SPE/One Step Plus, microTBS value with laser (27.09 MPa) was statistically higher than without laser (19.13 MPa), as well as for Adper Prompt L-Pop (22.85 and 13.78 Mpa; p < or = 0.01). The application of Nd:YAG laser to dentin provided an increase in the bond strength values for the Tyrian SPE/One Step Plus and Adper Prompt L-Pop adhesive systems, but did not influence the bond strength values of the Single Bond adhesive system.


Receptive fields in human visual cortex mapped with surface electrodes.
Most of our understanding of the functional organization of human visual cortex comes from lesion and functional imaging studies and by extrapolation from results obtained by neuroanatomical and neurophysiological studies in nonhuman primates. Although some single-unit and field potential recordings have been made in human visual cortex, none has provided quantitative characterization of spatial receptive fields (RFs) of individual sites. Here we use subdural electrodes implanted for clinical purposes to quantitatively measure response properties in different regions of human visual cortex. We find significant differences in RF size, response latency, and response magnitude for sites in early visual areas, versus sites in later stages of both the dorsal and ventral streams. In addition, we use this technique to estimate the cortical magnification factor in early human visual cortex. The spatial and temporal resolution of cortical surface recordings suggest that this technique is well suited to examine further issues in visual processing in humans.


Effect of reciprocating sliding speed on the tribological performance of nano SiC(p) reinforced Ni-metal matrix composites produced by electrocodeposition.
In the present work, Ni/SiC metal matrix composite (MMC) coatings were prepared from a modified Watt's type electrolyte containing nano-SiC particles by direct current (DC) plating method to increase wear resistance of the electro co-deposited Ni. SiC nano particles with average particle size of 0, 1-1 microm were co-deposited with nickel matrix on the steel substrates. For this purpose, several studies were carried out to optimize deposition parameters for specific applications. The depositions were controlled to obtain the specific thickness (between 175-200 microm) and particle volume fraction in the matrix (between 0.03 and 0.10). The hardness of the resultant coatings was measured and found to be 280-571 HV depending on the particle concentration in the electrolyte and therefore, particle volume in the Ni matrix. The tribological tests were performed by a reciprocating ball-on disk apparatus sliding against M50 steel ball (Ø10 mm). All the friction and wear tests were performed under the unlubricated conditions at room temperature and in the ambient air (relative humidity 55-65%). The wear tests were carried out at different sliding velocities of 50 mm/s, 100 mm/s and 150 mm/s by using a constant dead load of 1.0 N. It was detected that increasing sliding speed resulted to increase wear rate but decreasing friction coefficient due to change in wear mechanism. Increasing sliding speed showed formation of tribo induced oxides up to 20 g/l SiC(p) in the electrolyte and wear mechanism was controlled by temperature induced fatigue wear. Further increase in the SiC(p) in the electrolyte caused an abrasive type of the wear.


Understanding paroxysmal sympathetic hyperactivity after traumatic brain injury.
Paroxysmal sympathetic hyperactivity (PSH) is a condition occurring in a small percentage of patients with severe traumatic brain injury (TBI). It is characterized by a constellation of symptoms associated with excessive adrenergic output, including tachycardia, hypertension, tachypnea, and diaphoresis. Diagnosis is one of exclusion and, therefore, is often delayed. Treatment is aimed at minimizing triggers and pharmacologic management of symptoms. A literature review using medline and cinahl was conducted to identify articles related to PSH. Search terms included paroxysmal sympathetic hyperactivity, autonomic storming, diencephalic seizures, and sympathetic storming. Reference lists of pertinent articles were also reviewed and these additional papers were included. The literature indicates that the understanding of PSH following TBI is in its infancy. The majority of information is based on small case series. The review revealed treatments that may be useful in treating PSH. Nurses play a critical role in the identification of at-risk patients, symptom complexes, and in the education of family. Early detection and treatment is likely to decrease overall morbidity and facilitate recovery. Further research is needed to establish screening tools and treatment algorithms for PSH.


Late-Onset Nonthrombotic Left Common Iliac Vein Compression Secondary to Degenerative Lumbar Disc: A Case Report of May-Thurner Variant.
May-Thurner syndrome (MTS) refers to venous outflow obstruction caused by extrinsic compression of the left common iliac vein (LCIV) by the overlying pulsatile right common iliac artery against lumbar vertebrae. The classic clinical presentation is acute unilateral left leg painful swelling due to deep venous thrombosis in a young woman in the second or third decade of life. We present a case of a 66-year-old woman who presented with late-onset left leg swelling caused by nonthrombotic venous hypertension due to degenerative lumbar disc bulge leading to LCIV compression against the left common iliac artery which was confirmed by computed tomography and intravascular ultrasound. Our case highlights the importance of high index of suspicion for MTS in elderly patients with unilateral leg swelling and the importance of multimodality imaging for understanding the mechanism and appropriate treatment of MTS.


Post-transplant lymphoproliferative disorder of the adrenal gland after allogeneic hematopoietic stem cell transplantation: report of two cases and literature review.
Post-transplant lymphoproliferative disorder (PTLD) is one of the life-threatening complications after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT), and it is associated almost exclusively with Epstein-Barr virus (EBV). We herein report 2 cases of EBV-associated PTLD after allogeneic HSCT localized in the adrenal gland. Both patients developed adrenal tumor within 3 months after HSCT and were successfully treated with rituximab or tapering immunosuppressive agents. Both remained alive without recurrence. A literature review revealed 12 reported cases of PTLD involving the adrenal gland, but the adrenal gland was involved as one of the lesions of advanced-stage PTLD after SOT. To the best of our knowledge, this is the first report to show cases of isolated EBV-associated adrenal PTLD after HSCT. PTLD should be recognized as one of the causes of isolated adrenal tumor after HSCT.


Continuous infusion of epidural morphine in frostbite.
After frostbite injury, the phases of rewarming and progressive injury may cause intense pain for the patient. Although parenteral narcotic agents are the usual method of pain relief, they have well-described adverse effects such as heavy sedation, respiratory depression, and nausea and vomiting. In frostbite injury of the lower extremities, epidural blockade has the potential to provide good pain relief with fewer of those complications. However, the associated sympathetic blockade is believed by many clinicians to be of no benefit and by some to be potentially harmful. Epidural narcotics have the selective advantage of providing analgesia without sympathetic blockade. In this case report, the use of continuous epidural morphine during the first 24 hours after severe bilateral frostbite injury to the feet is described. The technique provided effective pain control, and no complications occurred. To our knowledge, use of continuous epidural morphine after frostbite injury has not been reported previously. Further use of this technique will be required to clarify its efficacy.


Secondary headaches in pregnancy and the puerperium.
Headache during pregnancy can be due to primary causes such as migraine but can also be a presenting symptom of secondary causes including life threatening conditions. This is a minireview of secondary causes of headache during pregnancy and the puerperium. Unique alterations in physiological and vascular functions as well as in the coagulation pathway which occur during pregnancy increase the risk of most of these secondary conditions which include preeclampsia, eclampsia, hemorrhagic stroke, cerebral venous, sinus thrombosis, reversible cerebral vascular syndrome, and posterior reversible encephalopathy. Marked increase in progesterone level in pregnancy is also associated with the growth of tumors such as meningiomas, as 70% of these tumors are positive for progesterone receptors and increase in size can lead to headache along with other neurological symptoms. Hemodynamic changes can lead to the growth of meningiomas as well. Although hormone producing pituitary tumors are usually not conducing to pregnancy, women with known pituitary tumors who do get pregnant may become symptomatic during pregnancy and develop secondary headache. Another rare cause of secondary headache during pregnancy is pituitary apoplexy. Although its occurrence is uncommon, it needs to be properly recognized and treated to avoid endocrine and visual complications. Other rare entities with increased incidence during the puerperium such postdural puncture headache will be also discussed. In summary, new onset headache during pregnancy deserves special attention because in the absence of proper recognition and treatment, secondary headache disorders can endanger the life of the mother and the fetus.


Antimicrobial susceptibility profiles and strain type diversity of Campylobacter jejuni isolates from turkeys in eastern North Carolina.
Campylobacter jejuni is one of the most common bacterial causes of human gastroenteritis, and recent findings suggest that turkeys are an important reservoir for this organism. In this study, 80 C. jejuni isolates from eastern North Carolina were characterized for resistance to nine antimicrobials, and strain types were determined by fla typing, pulsed-field gel electrophoresis (PFGE) with SmaI and KpnI, and (for 41 isolates) multilocus sequence typing (MLST). PFGE analysis suggested that many of the isolates (37/40 [ca. 93%]) in a major genomic cluster had DNA that was partially methylated at SmaI sites. Furthermore, 12/40 (30%) of the isolates in this cluster were completely resistant to digestion by KpnI, suggesting methylation at KpnI sites. MLST of 41 isolates identified 10 sequence types (STs), of which 4 were new. Three STs (ST-1839, ST-2132 and the new ST-2934) were predominant and were detected among isolates from different farms. The majority of the isolates (74%) were resistant to three or more antimicrobials, and resistance to ciprofloxacin was common (64%), whereas resistance to the other drug of choice for treatment of human campylobacteriosis, erythromycin, was never encountered. Most (33/34) of the kanamycin-resistant isolates were also resistant to tetracycline; however, only ca. 50% of the tetracycline-resistant isolates were also kanamycin resistant. Isolates with certain antimicrobial resistance profiles had identical or closely related strain types. Overall, the findings suggest dissemination of certain clonal groups of C. jejuni isolates in the turkey production industry of this region.


Acute low back pain: assessment and management.
Back pain is a common presenting problem in Australian general practice. Serious causes, however, are rare. Tumours, infections and fractures account for less than 1% of cases and can usually can be recognised or excluded by taking a careful history. Patients should expect a good outcome. This article summarises the management of acute low back pain and sets out the key points in history taking including alerting factors for serious disorders, and psychosocial factors that enable a rational management plan. A specific cause of pain need not be established for appropriate management to be instituted, with the active engagement of the patient as partner. Although no pattern of pain is diagnostic, a sudden onset of unremitting pain should be regarded as a 'red flag' to a serious underlying disorder. In accordance with evidence based principles, clinicians need to take into account previous experience, personal preferences, and cultural factors when recommending therapy for individual patients.


Identification of avian influenza virus subtype H9N2 in chicken farms in Indonesia.
Avian influenza virus subtype H9N2 (AIV-H9N2) has become established in domestic poultry in Asia and Africa. AIV-H9N2 has not been reported previously in Indonesia. Here we describe the presence of AIV-H9N2 in chicken farms in Indonesia. Ninety-nine cases were observed in various provinces in Indonesia. Clinical signs, pathologic lesions and egg production were recorded. Confirmation was made using virus isolation, reverse transcriptase PCR (RT-PCR), and sequencing. To construct hemaglutinin (HA) phylogeny, the secondary data of Eurasian lineages were downloaded from GenBank. For neuraminidase, five sequences with the highest similarities with every sequence found in this study were downloaded. Phylogeny was inferred using Neighbor-Joining method in MEGA6 package. Forty-nine AIV-H9N2-positive cases were observed, of which 35 were tested positive for AIV-H9N2 only. The age of the infected chickens was 43.17 ± 16.56 weeks, and their egg production was 35.85 ± 17.80% lower than before outbreak. BLAST search revealed that the nucleotide sequence of the HA-encoding gene identified in this study shared 98% sequence identity with that of A/Muscovy duck/Vietnam/LBM719/2014(H9N2), while its neuraminidase-encoding gene sequences shared 94%, 98%, and 100% identities with three different influenza viruses. The phylogeny shows that the HA of AIV-H9N2 found in this study forms distinct cluster with some Vietnam and China's sequence data. The NA sequence data form three distinct clusters. We conclude that AIV-H9N2 is widespread in many provinces in Indonesia. To lessen economic losses to the poultry industry, flock biosecurity and vaccination against this virus subtype should be implemented rapidly. Thorough and rigid AIV surveillance is paramount to prevent further veterinary and public health consequences of the circulation of this virus in Indonesia.


Behçet syndrome: is it one condition?
Behçet's syndrome (BS) is a disease of unknown etiology, and as such, there have been efforts to classify BS within the popular nosological identities of the times such as seronegative spondarthritides, autoimmune, and more recently autoinflammatory diseases. Current evidence suggests that BS does not easily fit into any one of these lumps, while on occasion, it might be impossible to tell BS from Crohn's disease, especially when the main clinical presentation is intestinal ulceration. There are distinct regional differences in disease expression of BS with fewer cases of intestinal disease in the Mediterranean basin and less severe eye disease and less frequent skin pathergy among patients reported from northern Europe or America. The clustering of symptoms, especially with the recently described increased frequency of the acne/arthritis cluster in familial cases, suggests that more than one pathological pathway is involved in what we call BS today. Supportive evidence for this contention also comes from the observations that (a) the genetic component is very complex with perhaps different genetic modes of inheritance in the adult and in the pediatric patients; and (b) there are differing organ responses to one same drug. For example, the anti-TNF agents successfully control the oral ulcers while they have no effect on the pathergy reaction.


Nanocomposites with Optimized Polytetrafluoroethylene Content as a Reinforcement Agent in PA12 and PLA for Material Extrusion Additive Manufacturing.
Herein, polytetrafluoroethylene (PTFE) is evaluated as a reinforcement agent in material extrusion (MEX) additive manufacturing (AM), aiming to develop nanocomposites with enhanced mechanical performance. Loadings up to 4.0 wt.% were introduced as fillers of polylactic acid (PLA) and polyamide 12 (PA12) matrices. Filaments for MEX AM were prepared to produce corresponding 3D-printed samples. For the thorough characterization of the nanocomposites, a series of standardized mechanical tests were followed, along with AFM, TGA, Raman spectroscopy, EDS, and SEM analyses. The results showed an improved mechanical response for filler concentrations between 2.0 and 3.0 wt.%. The enhancement for the PLA/PTFE 2.0 wt.% in the tensile strength reached 21.1% and the modulus of elasticity 25.5%; for the PA12/PTFE 3.0 wt.%, 34.1%, and 41.7%, respectively. For PLA/PTFE 2.0 wt.%, the enhancement in the flexural strength reached 57.6% and the modulus of elasticity 25.5%; for the PA12/PTFE 3.0 wt.%, 14.7%, and 17.2%, respectively. This research enables the ability to deploy PTFE as a reinforcement agent in the PA12 and PLA thermoplastic engineering polymers in the MEX AM process, expanding the potential applications.


Excess TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate.
Hypothyroidism in the young leads to irreversible growth failure. hyt/hyt Mice have a nonfunctional TSH receptor (TSHR) and are severely hypothyroid, but growth retardation was not observed in adult mice. We found that epiphysial cartilage as well as cultured chondrocytes expressed functional TSHR at levels comparable to that seen in the thyroid, and that addition of TSH to cultured chondrocytes suppressed expression of chondrocyte differentiation marker genes such as Sox-9 and type IIa collagen. Next, we compared the long bone phenotypes of two distinct mouse models of hypothyroidism: thyroidectomized (THYx) mice and hyt/hyt mice. Although both THYx and hyt/hyt mice were severely hypothyroid and had similar serum Ca(2+) and growth hormone levels, the tibia was shorter and the proliferating and hypertrophic zones in the growth plate was significantly narrower in THYx mice than in hyt/hyt mice. Supplementation of hyt/hyt mice thyroid hormone resulted in a wider growth plate compared with that of wild-type mice. Expressions of chondrocyte differentiation marker genes Sox-9 and type IIa collagen in growth plate from THYx mice were 52 and 60% lower than those of hyt/hyt mice, respectively. High serum TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate.


SOCIAL SELECTION AND THE EVOLUTION OF ANIMAL SIGNALS.
Social selection is presented here as a parallel theory to sexual selection and is defined as a selective force that occurs when individuals change their own social behaviors, responding to signals sent by conspecifics in a way to influence the other individuals' fitness. I analyze the joint evolution of a social signal and behavioral responsiveness to the signal by a quantitative-genetic model. The equilibria of average phenotypes maintained by a balance of social selection and natural selection and their stability are examined for two alternative assumptions on behavioral responsiveness, neutral and adaptive. When behavioral responsiveness is neutral on fitness, a rapid evolution by runaway selection occurs only with enough genetic covariance between the signal and responsiveness. The condition for rapid evolution also depends on natural selection and the number of interacting individuals. When signals convey some information on signalers (e.g., fighting ability), behavioral responsiveness is adaptive such that a receiver's fitness is also influenced by the signal. Here there is a single point of equilibrium. The equilibrium point and its stability do not depend on the genetic correlation. The condition needed for evolution is that the signal is beneficial for receivers, which results from reliability of the signal. Frequency-dependent selection on responsiveness has almost no influence on the equilibrium and the rate of evolution.


Upregulation of miR-137 reverses sorafenib resistance and cancer-initiating cell phenotypes by degrading ANT2 in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. More than 80% of patients with HCC are not good candidates for curative surgical resection due to advanced liver cirrhosis caused by underlying chronic hepatitis virus (B or C) infection. Sorafenib, an oral multikinase inhibitor, is the only approved agent for the treatment of advanced HCC. Although, sorafenib currently sets the new standard for advanced HCC treatment, tumor response rates are usually quite low. An understanding of the underlying mechanisms for sorafenib resistance is critical. In the present study, we found that adenine nucleotide translocator 2 (ANT2) was upregulated in sorafenib‑resistant HCC Huh7 cells (Huh7-R) and its overexpression promoted sorafenib resistance. ANT2 induced the formation of cancer-initiating cell (CIC) phenotypes and promoted metastasis-associated traits in the Huh7 cells. Silencing of miR-137 upregulated ANT2 protein expression in the Huh7 cells. miR-137 was downregulated in the Huh7-R cells, compared with that in the Huh7 cells and its restoration reversed sorafenib resistance in the Huh7-R cells. Restoration of miR-137 inhibited formation of CIC traits and attenuated the abilities of migration and invasion in the Huh7-R cells. Moreover, we demonstrated that high-intensity focused ultrasound (HIFU) in unresectable HCC upregulated serum miR-137. Combining HIFU and sorafenib may be a wise option for advanced and unresectable HCC.


Immunohistochemical evaluation of the effects of paraffin section storage on biomarker stability.
Environmental stresses can alter immunoreactivity of biomarkers in stored tissue sections. The effect of temperature and lighting on 49 cellular or microbial antigens was evaluated in 4 serial paraffin sections, cut 12 months, 10 months, 8 months, 5 months, 3 months, 1 month, 3 days, and 1 day before immunohistochemistry. Slides were stored at room temperature (RT) in the dark, at 4°C in the dark, at RT under fluorescent light, or at RT with windowpane exposure to sunlight. Immunohistochemistry was performed simultaneously in an automated immunostainer. Immunoreactivity was compared with that in the corresponding 1-day-old section and scored as 4 (<10% reduction), 3 (10%-25% reduction), 2 (26%-60% reduction), 1(>60% reduction), or 0 (no reactivity). Any loss of immunoreactivity was proportional to the tissue section age and was least in sections stored in the dark. Immunoreactivity was only completely lost in light-exposed sections and as early as 1 month for CD45. Other markers with complete loss of immunoreactivity were bovine viral diarrhea virus, CD18 (only with fluorescent light), CD31, CD68, canine parvovirus, chromogranins, and thyroid transcription factor-1. Markers with complete loss after light exposure also had reduced immunoreactivity when stored in the dark, as early as day 3. Eight markers (Bartonella spp, CD11d, high molecular weight cytokeratins, feline coronavirus, GATA-4, insulin, p63, progesterone receptor) had minimal decrease in immunoreactivity, regardless of treatment. In conclusion, light-induced antigen decay (tissue section aging) is antigen dependent and could explain unexpectedly weak or negative immunohistochemical reactions in stored paraffin sections.


Occurrence and distribution of endobacteria in the plant-associated mycelium of the ectomycorrhizal fungus Laccaria bicolor S238N.
Fluorescence in situ hybridization, associated with confocal laser scanning microscopy or epifluorescence microscopy with deconvolution system, has allowed the detection of a community of intracellular bacteria in non-axenic samples of the ectomycorrhizal fungus Laccaria bicolor S238N. The endobacteria, mainly alpha-proteobacteria, were present in more than half of the samples, which consisted of ectomycorrhizae, fungal mats and fruit bodies, collected in the glasshouse or in the forest. Acridine orange staining suggests that the endobacteria inhabit both live and dead fungal cells. The role of these endobacteria remains to be clarified.


P017 Increased Level of Immunoglobulin G in the Development of Adverse Reactions in Patients With Ulcerative Colitis.
Goal: To identify the relationship between the level of immunoglobulins G and E and the development of adverse reaction (AR) in patients with ulcerative colitis (UC) receiving original infliximab (IFХ) and infliximab biosimilar (BS). 35 UC patients with moderate to severe course of the disease (according to Truelove-Witts) who received maintenance therapy with IFХ at a standard dose of 5 mg/kg of body weight for a year were retrospectively analyzed. There were 16 men (45.7%), 19 women (54.3%). The average age is 34±4.2 years. The duration of the anamnesis was from 3 to 7 years. Patients were divided into 3 groups depending on the development of AR and the received biological drug, without taking into account concomitant anti-inflammatory therapy. The 1st group (n=14) alternated the introduction of the original IFХ and its BS; The 2nd group (n=7) consisted of patients alternating between the original IFХ and BS, in whom AR was registered; the 3rd group (n=14) received BS by one trade name. Using enzyme immunoassay, the level of immunoglobulins in the groups of patients was assessed. In the 1st and 3rd groups, AR was not observed. AR in 2nd group was characterized by: bronchospasm 3 (42.8%), Quincke's edema 1 (14.3%), urticaria 1 (14.3%), rhinitis 1 (14.3%), anaphylactic shock 1 (14.3%). In patients of 1st group, the level of IgE is 44.8 ± 5.1 IU/ml, IgG is 16.5 ± 1.7 g/l. In 2nd group -IgE-44.5 ± 11.7 IU / ml, IgG-26.1 ± 2.1 g/l, while in patients in group 3-IgE - 31.5 ± 3.04 IU/ml, IgG - 9.46 ± 1.01 g/l. It was reliably established that the highest level of IgG was observed in the 2nd group, while in the 3rd group it was minimal (p < 0.05). The IgG level in 1st group is higher than in 3rd group, although in both groups the IgG level was within the reference values. In all groups, the IgE value remained normal. AR on the background of therapy with IFL and biosimilars are not associated with an increase in the level of IgE, but are caused by an increase in the level of IgG. The alternation of the original drug and the biosimilar increases the risk of developing AR due to increased IgG levels. Treatment with a biosimilar by one trade name does not increase the risk of developing AR.


Dose accuracy of a durable insulin pen with memory function, before and after simulated lifetime use and under stress conditions.
The objective of this study was to assess the dose accuracy of NovoPen® 5 in delivering low, medium and high doses of insulin before and after simulated lifetime use. A secondary objective was to evaluate the durability of the pen and its memory function under various stress conditions designed to simulate conditions that may be encountered in everyday use of an insulin pen. All testing was conducted according to International Organization for Standardization guideline 11608-1, 2000 for pen injectors. Dose accuracy was measured for the delivery of 1 unit (U) (10 mg), 30 U (300 mg) and 60 U (600 mg) test medium in standard, cool and hot conditions and before and after simulated lifetime use. Dose accuracy was also tested after preconditioning in dry heat storage; cold storage; damp cyclical heat; shock, bump and vibration; free fall and after electrostatic charge and radiated field test. Memory function was tested under all temperature and physical conditions. NovoPen 5 maintained dosing accuracy and memory function at minimum, medium and maximum doses in standard, cool and hot conditions, stress tests and simulated lifetime use. The pens remained intact and retained dosing accuracy and a working memory function at all doses after exposure to variations in temperature and after physical challenge. NovoPen 5 was accurate at all doses tested and under various functionality tests. Its durable design ensured that the dose accuracy and memory function were retained under conditions of stress likely to be encountered in everyday use.


IPV, PrEP, and Medical Mistrust.
HIV pre-exposure prophylaxis (PrEP) is an effective HIV prevention method for women experiencing intimate partner violence (IPV). This study aimed to examine (1) relationships between physical, sexual, and psychological IPV and women's PrEP communication with a health care provider and domestic violence advocate; and (2) how IPV-specific medical mistrust modifies the association between IPV and PrEP communication. Data were from 2 studies conducted in Connecticut and Baltimore, MD on adult women experiencing IPV (N = 272). Logistic regressions examined associations between IPV, PrEP communication, and IPV-specific medical mistrust. The average age was 25.7. The most common identity was non-Hispanic black (37.1%), followed by non-Hispanic white (33.8%), Hispanic (20.6%), and non-Hispanic another racial group (8.5%). Higher severity of psychological IPV was associated with more embarrassment to initiate a PrEP discussion with a health care provider (P = 0.009) or domestic violence advocate (P = 0.026). However, women with more severe psychological IPV were more willing to accept a PrEP recommendation from a health care provider (P = 0.033) or domestic violence advocate (P = 0.044). IPV-specific medical mistrust modified the association between physical IPV and willingness to accept a PrEP recommendation by a domestic violence advocate, such that women with physical IPV were significantly less likely to accept a PrEP recommendation by a domestic violence advocate, but only for women with high IPV-specific medical mistrust (P = 0.021). PrEP initiation among women experiencing IPV may be strengthened by addressing and dismantling systems that perpetuate IPV-specific medical mistrust and stigma against IPV survivors.


Thiolated pyrimidine nucleotides may interfere thiol groups concentrated at lipid rafts of HIV-1 infected cells.
Upon HIV infection, cells become activated and cell surface thiols are present in increased number. Earlier we demonstrated in vitro anti-HIV effect of thiolated pyrimidine nucleotide UD29, which interferes thiol function. To further analyse the redox processes required for HIV-1 entry and infection, toxicity assays were performed using HIV-1 infected monolayer HeLaCD4-LTR/ β-gal cells and suspension H9 T cells treated with several thiolated nucleotide derivatives of UD29. Selective cytotoxicity of thiolated pyrimidines on HIV-1 infected cells were observed. Results indicate that thiolated pyrimidine derivates may interfere with -SH (thiol) groups concentrated in lipid rafts of cell membrane and interacts HIV-1 infected (activated) cells resulting in a selective cytotoxicity of HIV-1 infected cells, and reducing HIV-1 entry.